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2 Take Home Message Exploratory (e.g., pharmacometric) analyses are often used to make regulatory decisions –Decisions are not entirely driven by the pre-specified statistical analysis Need for change –Integrate strengths of both approaches Think How exploratory analyses can help drug development? –Opportunities for collaboration between pharmacometricians and statisticians are abundant Think about How can I facilitate this collaboration?

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7 Equivocal Evidence of Effectiveness Pivotal Studies DB#1 Dbl-blind (DB) Randomized PBO Controlled Dose Titration N=75 P<0.05 1 (withdrawal) DB#2 Dbl-blind (DB) Randomized PBO Controlled Dose Withdrawal N=30 P>0.05 1 Agency at this point can ask for more evidence (one or more studies) OR Investigate further across the clinical trial database whether there is a consistent signal of effectiveness or not 1 change in score at the end of study

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19 Published Data Mean (SD) of Total UPDRS scores for patients with Parkinsons disease treated with levodopa alone or in combination with selegiline for 5 years and during the one-month washout period The vertical line represents 2 months Selegiline ( 5 years) Eur.J.Neurology, 1999, 6: 539-547

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23 Take Home Message Exploratory (e.g., pharmacometric) analyses are often used to make regulatory decisions –Decisions are not entirely driven by the pre-specified statistical analysis Need for change –Integrate strengths of both approaches Think How exploratory analyses can help drug development? –Opportunities for collaboration between pharmacometricians and statisticians are abundant Think about How can I facilitate this collaboration?